Enhanced Ca2+ -induced contractions and attenuated α-adrenoceptor responses in resistance arteries from rats with congestive heart failure

Aim: The aim of the present study was to examine the role of Ca2+ -mediated contractile responses in isolated mesenteric resistance arteries from rats with congestive heart failure (CHF). Methods: Heart failure was induced by ligation of the left coronary artery. Rats exposed to the same surgical procedure except ligation served as controls (Sham). The following experiments were conducted: (1) passive increase in radial stretch (the length–tension relationship) in Ca2+ -free and in depolarizing high K+- solution; (2) the contractile responses to external application of Ca2+ and high K+ -solutions in the presence of nifedipine and phentolamine; and (3) a histological evaluation of CHF and Sham vessels. Results: The length–tension induced response in Ca2+ -free buffer solution was significantly lower in arteries from CHF rats, starting at a very low tension (0.9 ± 0.2 mN/mm for heart failure and 1.7 ± 0.2 mN/mm for Sham). This difference, but at a higher degree of stretch, was also present in K+ -activated vessels. The external application of Ca2+ in K+ -depolarized vascular segments in the presence of phentolamine (1 μM) induced an enhanced contractile response in arteries from CHF rats compared with Sham (4.8 ± 0.3 mN/mm and 3.6 ± 0.6 mN/mm, respectively, P = 0.059). In the absence of phentolamine the reverse response was found (4.0 ± 0.4 mN/mm and 5.7 ± 0.3 mN/mm for CHF vs. Sham respectively, P = 0.035). Application of increasing concentrations of K+ -solution induced a stronger contractile response in Sham compared with CHF arteries (Sham 4.9 ± 0.4 and heart failure 4.0 ± 0.3, P = 0.04). Microscopic examination of vessels yielded no difference in gross morphology, media thickness or wall to lumen ratio between CHF and Sham arteries. Conclusion: The results indicate an attenuation of α-adrenoceptors and a difference of Ca2+ -mediated vascular contractility in resistance arteries of congestive heart failure rats.